1. Field of the Invention
The invention relates generally to medical implants, especially medical implants eliciting a benign body response.
2. Description of the Related Art
Ultra-high molecular weight polyethylene (“UHMWPE”) is the most commonly used bearing material in total joint replacements and was introduced by John Charnley in the early 1960s (The UHMWPE Handbook, edited S. Kurtz, Elsevier, 2004). Since then, a wide variety of applications have been developed in the total joint arthroplasty, as a result of the material's high toughness and good mechanical properties. UHMWPE is one of the only polymers that is used in its pure form and does not contain additives (ASTM F 648-07).
Although “conventional” UHMWPE has an excellent clinical record, the maximum lifetime of implant systems is restricted due to the wear particles released from the UHMWPE bearing surface (Willert H. G., Bertram H., Buchhorn G. H., Clin Orthop 258, 95, 1990). The negative biological effects of wear particles are considered to be the most important limiting factors for a long implant life. The liberation of sub micron size wear debris into human tissue leads to chronic inflammation. Continuous inflammation caused by UHMWPE particles activates inflammatory cells (macrophages) that stimulate bone resorptive cells (osteoclasts) and eventually a loosening of the implant.
In the 1970s, highly crosslinked UHMWPEs have been introduced with the intention of improving the wear resistance of the material (Oonishi H., Kadoya Y., Masuda S., Journal of Biomedical Materials Research, 58, 167, 2001; Grobbelaar C. J., du Plessis T. A., Marais F., The Journal of Bone and Joint Surgery, 60-B, 370, 1978). The UHMWPE materials were gamma irradiated at high doses up to 100 Mrad, this is in contrast to gamma sterilized UHMWPE which typically receive a dose ranging between 2.5 and 4.0 Mrad. The high doses were used to promote the crosslinking process in the material and thereby increase the wear resistance. Hence, the crosslinking process led to a reduction of the wear particles and therefore also to a reduction of malign body response reactions. A disadvantage of the highly crosslinked materials was that there were still free radicals present in the material, potentially leading to oxidative degradation.
The energy of the gamma rays is sufficient to break some of the carbon-carbon or carbon-hydrogen bonds of the polyethylene chains resulting in the formation of free radicals. These radicals partially recombine but some of them are long-living and can react with oxygen present in, or diffusing into, the packaging surrounding the implant (Costa L., Jacobson K., Bracco P., Brach del Prever. E. M., Biomaterials 23, 1613, 2002). The oxidative degradation reactions lead to embrittlement of the material and therewith reduce the mechanical properties of the material and might lead to fracture of the implant (Kurtz S. M., Hozack W., Marcolongo M., Turner J., Rimnac C., Edidin A., J Arthroplasty 18, 68-78, 2003).
Quenching of free radicals by heat treatment either above or below the crystalline melt temperature of UHMWPE has been known for a long time (S. Kurtz, The UHMWPE Handbook, Elsevier Academic Press, 2004, p. 112). Hence, in the 1990's, highly crosslinked materials were developed that were thermally treated (annealed or remelted) after the irradiation process to combine enhanced wear with oxidative stability since the residual free radicals were quenched during the thermal treatment process.
Despite the lower wear rate, and therefore lower volume of wear particles, of highly crosslinked UHMWPE, which was confirmed by clinical studies, the osteolysis did not disappear completely. In several studies, osteolytic regions or radiolucent zones were described for implant systems using highly crosslinked UHMWPE (J. A. D'Antonio et al., Clinical Orthopaedics and Related Research, 441, 2005; C. A. Engh et al., The Journal of Arthroplasty, 21 (6 Suppl. 2), 2006; G. Digas et al., Clinical Orthopaedics and Related Research, 417, 2003). Hence, even the low amount of wear particles generated by highly crosslinked UHMWPE is able to start an inflammatory reaction which finally leads to osteolysis.
Curcumin, a component of the Indian spice turmeric, is well documented for its medicinal properties in Indian medicine. Apart from other beneficial properties, curcumin is described to have anti-oxidant and anti-inflammatory properties (R. K. Maheshwari et al., Life Sciences, 78 (18), 2006; A. Sahu, Acta Biomaterialia, Article in Press, 2008; S. Merell et al., Presentation at the World Biomaterials Conference, Amsterdam 2008; The University of Texas MD Anderson Cancer Center, Webpage: http://www.mdanderson.org/departments/cimer/).
Other literature studies describe beneficial properties of different substances: In a very recent study, quercetin was described to promote bone formation when mixed into collagen matrix (R. W. K. Wong et al., Journal of Orthopaedic Research, 26 (8), 2008). Another study describes a reduced osteolysis induced by tumor extracts by the addition of diphosphonates (A. Jung et al., Schweiz. Med. Wochenschr., 109 (47), 1979. The same effect of diphosphonates was shown in another study (C. S. B. Galasko et al., Paper presented at the Fourth Tripartite Surgical Meeting, Oxford, England, 5-7 Jul. 1979).